The present invention is concerned with a system for automatically carrying out testing using a cascade impactor.
Cascade impactors are in themselves well known. They are used for analysis of aerosols, and more specifically for obtaining information about the size distribution of particles in an aerosol. Particulate material can be entrained in a gas flow to form an aerosol for analysis. The aerosol is passed through a sequence of impaction stages, larger particles tending to collect in the earlier stages and smaller particles in the later ones. In this context, the term “aerosol” is to be understood to refer to particles suspended in a fluid. The fluid in question is typically a gas although in principle it could be a liquid. The particles may be solid, liquid, or a mixture of the two.
Cascade impactors can be used for a range of purposes including for example analysis of air pollution. However, an application of particular importance in the present context involves testing of drug delivery devices such as inhalers. These are used to deliver a controlled dose of a drug to the respiratory tract of a patient. Typically the target area is the lungs, or particular areas thereof. A proportion of the dose will inevitably be retained in the mouth and throat. Inhalers are very commonly used in the treatment of asthma, but can also be used for delivery of drugs to treat other diseases, respiratory or otherwise. To demonstrate that the correct dose is being dispensed, analysis is required of particle size in the inhaler output. In a dry powder inhaler the pharmaceutical material is stored in powder form, but air drawn through the inhaler in use causes the powder to be entrained in an aerosol. There are other forms of inhaler which are relevant for present purposes including the pressurised metered dose inhaler (pMDI) in which the drug formulation comprises drug which is suspended or dissolved in a propellant (e.g. HFA 134a or HFA 227), the formulation optionally including one or more excipients, such as a surfactant. The propellant is used to create an aerosol which is then entrained in the inspiratory airflow of the patient. Nebulizer devices may also be tested using impactors of the type referred to herein. Pharmaceutical companies have a requirement to carry out batch testing on large numbers of inhalers. It is known to carry out such testing by firing the inhaler into an impactor. The powdered pharmaceutical material collects upon component parts of the impactor, from which it is then recovered for analysis. This recovery has traditionally been done by solvent rinsing in a manual process, but the labour involved is considerable and the process is slow. Hence it is highly desirable to automate impactor testing.
A form of impactor sometimes referred to as the “next generation impactor” has been developed by MSP Corporation of Minneapolis and is described for example in UK Patent 2351155. It has a tray defining multiple side-by-side impaction cups, with an impactor head to be placed upon the tray defining transfer passages from one cup to another. A nozzle plate positioned between the cup tray and the impactor head forms nozzles at the outlet of each transfer passage, the nozzles having successively smaller openings for through-passage of the aerosol, and particles with diminishing sizes are trapped in the successive impaction cups. The next generation impactor needs, after it has been dosed with one or more samples from an inhaler, to be disassembled to permit recovery of sample material from its component parts, by immersing the relevant surfaces in solvent to obtain solutions containing the sample material. This form of sample recovery is carried out on the individual cups, and also on an induction port through which the impactor interfaces with the inhaler, and in some cases on an optional preseparator used to remove the largest particles from the aerosol before it enters the impactor itself. After the recovery of the sample material, components of the impactor need to be washed and re-assembled ready for re-use.
Some details of an automation system for an impactor of this type are to be found in published United States Patent Application 2004/0250634, assignee MSP Corporation, and also in published International Patent Application WO 02/063277, applicant MSP Corporation. Both documents describe, in somewhat schematic terms, a system for carrying out repeated impaction testing automatically. However, significant technical challenges remain in practically implementing such a system.